Analysis finds corticosteroids cut risk of death in critically ill COVID-19 patients

Results of a meta-analysis published Wednesday in JAMA suggest that the use of systemic corticosteroids in critically ill patients with COVID-19 is associated with lower 28-day all-cause mortality compared to usual care or placebo. Study author Jonathan Sterne noted that the benefit was seen regardless of age, sex or how long patients had been ill for.

"Steroids are a cheap and readily available medication, and our analysis has confirmed that they are effective in reducing deaths amongst the people most severely affected by COVID-19," Sterne remarked. The latest findings follow results from the RECOVERY study released in June which found that low-dose dexamethasone reduced the risk of death by up to one third in hospitalised patients with severe respiratory complications of COVID-19.

Analysis of seven studies

The meta-analysis in JAMA pooled data from seven randomised trials, including RECOVERY, that evaluated corticosteroids in 1703 critically ill patients with COVID-19. Among the participants, 678 patients had been randomised to receive systemic dexamethasone, hydrocortisone or methylprednisolone, while the remaining 1025 were administered usual care or placebo. The median age was 60 years, and 71% of the subjects included in the analysis were male. Dexamethasone and hydrocortisone were tested in three trials each, and methylprednisolone in one. The trials were conducted in 12 countries from February 26 to June 9, with the date of final follow-up on July 6.

Researchers found there were 222 deaths among the corticosteroid-treated patients and 425 deaths among those given usual care or placebo, for a 0.66 summary odds ratio. The authors noted that this corresponds to an absolute mortality risk of 32% with corticosteroids compared with an assumed mortality risk of 40% with usual care or placebo. When broken down by treatment, dexamethasone produced the strongest benefit with a 36% drop in deaths compared with usual care or placebo, followed by hydrocortisone and methylprednisolone, which reduced mortality by 31% and 9%, respectively.

Meanwhile, among the six trials that reported serious adverse events, 64 events occurred among 354 patients randomised to corticosteroids and 80 events occurred among 342 patients randomised to usual care or placebo. "Adverse events varied across trials, but there was no suggestion that the risk of serious adverse events was higher in patients assigned to corticosteroids except for the two smallest trials," the authors noted.

Findings 'instantly usable'

Commenting on the results, Martin Landray, an investigator on the RECOVERY trial, said the new data mean doctors can safely switch to using corticosteroids. "These results are clear, and instantly usable in clinical practice," he noted, added "among critically ill patients with COVID-19, low-dose corticosteroids...significantly reduce the risk of death." Howard Bauchner, editor-in-chief at JAMA, remarked that "clearly, now steroids are the standard of care."

Based on the latest evidence, the World Health Organization issued new treatment guidance strongly recommending steroids to treat severely and critically ill COVID-19 patients. However, the agency warned against indiscriminate use of steroids, noting that patients who are not severely ill are unlikely to benefit and may suffer side effects.

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